太子参多糖对缺血再灌注损伤模型大鼠心肌细胞凋亡的抑制作用研究

Study on the Inhibitory Effects of Pseudostellaria heterophylla Polysaccharide on Myocardial Apoptosis of Ischemia-reperfusion Injury Model Rats

目的:研究太子参多糖对心肌缺血再灌注损伤模型大鼠心肌细胞凋亡的抑制作用,并探讨其作用机制。方法:取SD大鼠72只,随机分为假手术组、模型组、阳性药物组(硝苯地平片,5 mg/kg)和太子参多糖低、中、高剂量组(7.5、15、30 g/kg),每组12只。假手术组和模型组大鼠均灌胃水,其余组大鼠分别灌胃相应药物7 d后,全部大鼠以结扎左冠状动脉前降支使心肌缺血30min后再灌注120 min的方法建立缺血再灌注损伤模型(其中仅假手术组大鼠穿线但不结扎)。采用苏木精-伊红染色法,在显微镜下观察大鼠心肌组织病理学变化;采用TUNEL法检测大鼠心肌细胞凋亡情况;采用Western Blot法检测心肌组织中Bax、Bcl-2和胱天蛋白酶3(Caspase-3)蛋白表达水平。结果:与模型组比较,太子参多糖各剂量组大鼠心肌组织的病理学变化程度明显减轻,心肌细胞凋亡数量明显减少;太子参多糖各剂量组大鼠心肌组织中Bax蛋白表达水平以及Bax/Bcl-2蛋白表达水平比值均显著降低,低、中剂量组Caspase-3蛋白表达水平均显著降低,高剂量组Bcl-2蛋白表达水平显著升高,差异均有统计学意义(P<0.05或P<0.01)。结论:太子参多糖能显著减轻心肌缺血再灌注损伤模型大鼠的心肌组织损伤,并抑制心肌细胞凋亡,该作用可能是通过下调促凋亡相关蛋白Bax、Caspase-3和上调抑凋亡相关蛋白Bcl-2的表达来实现的。

OBJECTIVE：To study the inhibitory effects of Pseudostellaria heterophylla polysaccharide on myocardial apoptosis of ischemia-reperfusion injury（IRI） model rats,and to investigate its mechanism. METHODS：Totally 72 SD rats were selected and randomly divided into sham operation group, model group, positive drug group（Nifedipine tablets, 5 mg/kg） and P.heterophylla polysaccharide high-dose,medium-dose and low-dose groups（7.5,15,30 g/kg）,with 12 rats in each group. Sham operation group and model group were given water intragastrically,and other groups were given relevant medicine intragastrically for 7 d. The IRI model was established by ligating the anterior descending branch of left coronary artery,reperfusing 120 min after30 min of myocardial ischemia（not occluded only in sham operation group）. HE staining was used to observe the pathological changes of myocardium in rats under microscope. Myocardial apoptosis was detected by TUNEL method. The protein expression levels of Bax,Bcl-2 and Caspase-3 in myocardial tissue were detected by Western blot method. RESULTS：Compared with model group,pathological changes of myocardial tissue were relieved significantly in P. heterophylla polysaccharide groups,while the number of myocardial cell apoptosis was decreased significantly. The protein expression levels of Bax,the protein expression ratio of Bax and Bcl-2 in myocardial tissue were decreased significantly in P. heterophylla polysaccharide groups;those of Caspase-3 in P. heterophylla polysaccharide low-dose and medium-dose groups were decreased significantly;those of Bcl-2 were increased significantly in P. heterophylla polysaccharide high-dose group, with statistical significance（P〈0.05）. CONCLUSIONS： P.heterophylla polysaccharide can significantly relieve myocardial tissue injury and inhibit myocardial apoptosis in IRI model rats. Its mechanism may be associated with reducing proapoptotic protein Bax and Caspase-3 and raising apoptotic protein Bcl-2 expression.